Evaluation of hypersensitivity to anthraquinone-related substances

Evaluation of hypersensitivity to anthraquinone dyes, which are widely used as color additives, was performed in guinea pigs. In animals sensitized with 1% commercial-grade D&C Green No. 6 (Quinizarin Green SS, CI61565), subsequent challenge with the same dye showed a dose-dependent hypersensitivity reaction, whereas challenge with D&C Green No. 6 purified by recrystallization did not. Guinea pigs sensitized with commercial-grade D&C Green No. 6 showed a positive reaction to challenge with quinizarin, an intermediate in dye synthesis, but not to p-toluidine, another intermediate. It was confirmed that quinizarin itself induced hypersensitivity. The cross-reactivity of four kinds of purified dyes, in which the quinizarin contents were 1.2ppm or less, was evaluated. Purified D&C Green No. 5 (Alizarin Cyanin Green F, CI61570), D&C Green No. 6 and Ext. D&C Violet No. 2 (Alizurol Purple, CI60730) did not produce a hypersensitivity response, while D&C Violet No. 2 (Alizurin Purple SS, CI60725) did. We found that D&C Green No. 5, D&C Green No. 6 and Ext. D&C Violet No. 2 do not intrinsically induce hypersensitivity, and we conclude that the reaction to challenge with the commercial-grade dyes is due to quinizarin contaminating them. In contrast, D&C Violet No. 2 per se induced hypersensitivity. A structure-activity study indicated that 1-hydroxyl and 4-hydroxyl groups in the anthraquinone structure are key factors in hypersensitivity induction by anthraquinone-related compounds.